amrubicin and Carcinoma--Neuroendocrine

Although the same treatment strategy as used for small cell lung cancer, including second-line chemotherapy, is generally applied to metastatic neuroendocrine carcinoma (NEC) and mixed adenoneuroendocrine carcinoma (MANEC) of the gastrointestinal tract (GIT; GIT-NEC/MANEC), the efficacy of amrubicin (AMR) for GIT-NEC/MANEC is not well known. We retrospectively analyzed platinum-refractory GIT-NEC/MANEC patients who received AMR between February 2004 and July 2012 at the National Cancer Center Hospital. The AMR dose administered was 30-45 mg/m on days 1-3 every 3-4 weeks. The overall response rate according to Response Evaluation Criteria in Solid Tumors guidelines, version 1.0, progression-free survival, overall survival, and adverse events by National Cancer Institute-Common Terminology Criteria for Adverse Events guidelines, version 4.0 were evaluated. Nineteen patients received AMR. The response rate for 16 assessable patients was 18.8% (95% confidence interval, 4.1-45.7), the median progression-free survival was 3.8 months (2.3-5.3), and the median overall survival was 7.7 months (7.1-8.2). Grade 3/4 neutropenia occurred in 52.6% of patients and febrile neutropenia occurred in 10.5%. Other nonhematological toxicities were mild and treatment-related deaths were not observed. AMR may have a modest effect, with tolerable toxicities, on patients with platinum-refractory GIT-NEC/MANEC. Further prospective evaluations are warranted.

Topics: Adult; Aged; Aged, 80 and over; Anthracyclines; Antineoplastic Agents; Carcinoma, Neuroendocrine; Disease-Free Survival; Female; Gastrointestinal Neoplasms; Humans; Male; Middle Aged; Platinum Compounds; Retrospective Studies; Treatment Outcome

An 86‒year‒old man with chronic kidney disease underwent surgical resection for combined large‒cell neuroendocrine carcinoma of the left lower lobe of the lung(pT2aN1M0, stage ⅡB). Five months later, multiple liver and bone metastases and mediastinal lymph node recurrence were detected. After 9 courses of amrubicin monotherapy(32 mg/m2 for 3 consecutive days), his tumor marker levels normalized, and radiological examination revealed a complete tumor response. Adverse events occurred, but they were tolerable except a decrease in the neutrophil count. The patient remained in good condition for several months but died of tumor relapse 22 months after the initial recurrence. Amrubicin monotherapy was considered to be one of the treatment choices for recurrent large‒cell neuroendocrine carcinoma of the lung in elderly patients.

Topics: Aged; Aged, 80 and over; Anthracyclines; Carcinoma, Neuroendocrine; Humans; Lung; Lung Neoplasms; Male; Neoplasm Recurrence, Local

Standard regimens for extrapulmonary neuroendocrine carcinomas(EPNEC)are not established. Treatment used for small cell lung cancer is also used for EPNECs. Amrubicin(AMR) monotherapy is used as salvage therapy for small cell lung cancer, but its efficacy in EPNEC is not clear. The aim of this study was to estimate the efficacy of AMR monotherapy in EPNEC. We retrospectively investigated patients with EPNEC who received first-line platinum-based chemotherapy between April 2007 and March 2019. The time to treatment failure(TTF)and the efficacy and toxicity was analyzed in the patients who received AMR monotherapy. Among 43 patients with EPNEC, 14(13 males, one female; median age, 58 years)received AMR monotherapy. Primary site included the pancreas(n=3), stomach(n=3), rectum(n=1), anal canal(n=1), salivary glands(n= 1), urothelial(n=1), bladder(n=1), prostate(n=1), and 2 patients had primary unknown cancer. Pathological type included small cell(n=4), large cell(n=2), and other types(n=8). Prior chemotherapy comprised CDDP plus CPT-11(n =5), CDDP plus ETP(n=2), and CBDCA plus ETP(n=6). The median TTF was 49(20-61)days. One patient had a partial response and the disease control rate was 33%. The common adverse events of >Grade 3 were leukopenia(69%), neutropenia(62%), and febrile neutropenia(23%). AMR monotherapy was clinically effective and safe for EPNEC.

Topics: Anthracyclines; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Neuroendocrine; Female; Humans; Lung Neoplasms; Male; Middle Aged; Platinum; Retrospective Studies; Treatment Outcome

Extrapulmonary neuroendocrine carcinoma (NEC) is a rare disease, and there is no standard chemotherapy. A 73-year-old man was diagnosed with advanced gastric NEC. He received chemotherapy of irinotecan plus cisplatin, and amrubicin monotherapy. After failure of second-line chemotherapy, he received ramucirumab plus paclitaxel; this treatment was chosen because vascular endothelial growth factor 2 was strongly expressed in the tumor endothelial cells. After two cycles, his NEC had markedly reduced in size, and he continued with this treatment for over eight months. In this case, the combination of an anti-angiogenic inhibitor and a cytotoxic agent was highly effective for gastric NEC.

Topics: Aged; Anthracyclines; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoma, Neuroendocrine; Cisplatin; Humans; Irinotecan; Male; Paclitaxel; Ramucirumab; Stomach Neoplasms

The aim of this study was to investigate the clinical usefulness of amrubicin therapy for patients with non-gastrointestinal (GI) non-pancreatic extrapulmonary neuroendocrine carcinoma (EP-NEC).. The medical records of patients from the 2 participating institutions were retrospectively reviewed. The eligibility criteria were: patients with non-GI non-pancreatic EP-NEC who received amrubicin monotherapy after platinum-based chemotherapy. Patients in whom the platinum-free interval (interval between the last day of platinum administration and the first subsequent documentation of disease progression) was 90 days or longer were classified into the platinum-sensitive group.. The study was conducted in a total of 13 patients identified as eligible. The response rate was 45.4% (5/11). The median progression-free survival and overall survival were 6.0 and 10.6 months, respectively. A platinum-free interval of ≥90 days was identified as a significant predictor of a longer progression-free survival time. Grade 3 or 4 neutropenia was observed in 61.5% (8/13) of the patients. One patient died of treatment-related febrile neutropenia.. Amrubicin monotherapy as second-line chemotherapy after failure of first-line platinum-based chemotherapy showed good efficacy in patients with non-GI non-pancreatic EP-NEC. Neutropenia was encountered as the most serious adverse event.

Topics: Adult; Aged; Aged, 80 and over; Anthracyclines; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Neuroendocrine; Disease-Free Survival; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neutropenia; Retrospective Studies; Salvage Therapy; Treatment Outcome

Extrapulmonary neuroendocrine carcinomas (EPNEC) are rarely observed and are associated with poor outcomes. Based on the clinicopathological similarity, treatment used for small cell lung carcinoma has also been employed for EPNEC, but the response to such therapy has not been well examined. The goal of this study was to investigate amrubicin (AMR) monotherapy as a salvage therapy for EPNEC arising from digestive organs.. Patients with EPNEC of the digestive organs who had prior platinum-based chemotherapy and were subsequently treated with AMR between July 2005 and December 2013 at any one of four institutions were retrospectively examined to characterize the safety and efficacy of AMR.. Thirteen patients (ten males, three females; median age 64 years) were examined. Primary cancer sites included stomach (n = 6), rectum (n = 3), esophagus (n = 2), liver (n = 1) and pancreas (n = 1). Prior irinotecan- and etoposide-containing chemotherapies were used in ten and six patients, respectively. Median initial dose of AMR was 40 mg/m(2)/day for three consecutive days, and median of treatment cycles was 4 (range 1-9). The objective response rate (ORR) was 38.5%. Median progression-free survival (PFS) and overall survival (OS) were 107 (range 22-275) and 215 days (range 71-535), respectively. Common severe adverse events (grade 3/4) were neutropenia (84.6%) and febrile neutropenia (30.8%). Patient with longer platinum-free interval (>90 days) exhibited longer PFS and OS than those with shorter platinum-free interval (190 vs. 63 days and 348 vs. 145 days, respectively).. AMR showed evidence of clinical activity and safety when used for the treatment of EPNEC. It might be especially useful for populations with sensitive relapse.

Topics: Aged; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Neuroendocrine; Cisplatin; Digestive System Neoplasms; Disease-Free Survival; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Retrospective Studies; Salvage Therapy

We present the case of a Japanese man in his 60s with duodenal neuroendocrine carcinoma with distant metastases. Chemotherapy with irinotecan plus cisplatin was initiated as a first-line regimen. However, disease progression was observed after only two cycles. Therefore, amrubicin was administered as a second-line chemotherapy. The patient showed a long-term effect of amrubicin therapy, and the best response was a partial response after seven cycles. For duodenal neuroendocrine carcinoma, amrubicin therapy can be considered an effective treatment option as salvage chemotherapy.

Topics: Aged; Anthracyclines; Antineoplastic Agents; Biomarkers, Tumor; Biopsy; Carcinoma, Neuroendocrine; Duodenal Neoplasms; Duodenoscopy; Humans; Immunohistochemistry; Male; Middle Aged; Salvage Therapy; Time Factors; Tomography, X-Ray Computed; Treatment Outcome

No standard chemotherapy has been established yet for large-cell neuroendocrine carcinoma of the lung. Amrubicin is active for both small cell and non-small cell lung cancers, but its activity for large-cell neuroendocrine carcinoma is still unknown.. From January 2002 to December 2009, 18 patients with previously treated advanced large-cell neuroendocrine carcinoma received amrubicin monotherapy. The efficacy and toxicity of the treatment were analyzed retrospectively.. The patients comprised 17 males and one female with a median age of 62 years (range, 51-77). Fourteen and four patients had a performance status of 0-1 and 2, respectively. Thirteen (72%) patients had received one prior chemotherapy, while the others had received two or more chemotherapies. All the patients had received platinum-based chemotherapy before the amrubicin treatment. A total of 63 cycles of amrubicin chemotherapy was administered in the 18 patients, with a median number of cycles per patient of 2.5 (range, 1-10). The median dose of amrubicin in the 63 cycles was 40 (range, 30-45) mg/m(2)/day for 3 days. Grades 3-4 neutropenia, thrombocytopenia and anemia were seen in 89, 17 and 22% of the patients, respectively. Grade 3 febrile neutropenia occurred in 33% of the patients. Non-hematological toxicity was generally mild and manageable. There were five cases of partial response, six of stable disease and six of progressive disease among the 18 patients, yielding an objective response rate of 27.7%. The median progression-free and overall survivals of the patients were 3.1 and 5.1 months, respectively.. Amrubicin was potentially active against previously treated large-cell neuroendocrine carcinoma.

Topics: Aged; Anthracyclines; Antineoplastic Agents; Carcinoma, Large Cell; Carcinoma, Neuroendocrine; Disease-Free Survival; Drug Administration Schedule; Female; Humans; Lung Neoplasms; Male; Middle Aged; Retrospective Studies; Treatment Outcome